Light generating device for intravascular use

ABSTRACT

Light generating devices for illuminating portions of vascular tissue, to render photodynamic therapy. In one embodiment, a light source array preferably including a plurality of light emitting diodes, a focusing lens, and a light diffusing element are included in a distal end of a catheter. A balloon is optionally provided to interrupt blood flow that can block the transmission of light, and to center the apparatus in a blood vessel. Optical fibers optionally direct light from the light source to the diffusing element. The light source array can have a radial or linear configuration and can produce more than one wavelength of light for activating different photoreactive agents. Linear light source elements are particularly useful to treat elongate portions of tissue in a vessel. One embodiment intended for use with a conventional balloon catheter integrates light sources into a guidewire.

RELATED APPLICATIONS

This application is a divisional of a copending patent application Ser.No. 10/799,357, filed on Mar. 12, 2004, which itself is based on a priorcopending provisional application Ser. No. 60/455,069, filed on Mar. 14,2003, the benefit of the filing dates of which are hereby claimed under35 U.S.C. §119(e) and 120.

BACKGROUND

Photodynamic therapy (PDT) is a process whereby light of a specificwavelength or waveband is directed to tissues undergoing treatment orinvestigation, which have been rendered photosensitive through theadministration of a photoreactive or photosensitizing agent. Thus, inthis therapy, a photoreactive agent having a characteristic lightabsorption waveband is first administered to a patient, typically byintravenous injection, oral administration, or by local delivery to thetreatment site. Abnormal tissue in the body is known to selectivelyabsorb certain photoreactive agents to a much greater extent than normaltissue. Once the abnormal tissue has absorbed or linked with thephotoreactive agent, the abnormal tissue can then be treated byadministering light of an appropriate wavelength or wavebandcorresponding to the absorption wavelength or waveband of thephotoreactive agent. Such treatment can result in the necrosis of theabnormal tissue.

PDT has proven to be very effective in destroying abnormal tissue suchas cancer cells and has also been proposed for the treatment of vasculardiseases, such as atherosclerosis and restenosis due to intimalhyperplasia. In the past percutaneous transluminal coronary angioplasty(PTCA) has typically been performed to treat atheroscleroticcardiovascular diseases. A more recent treatment based on the use ofdrug eluting stents has reduced the rate of restenosis in some diseasedvessels. As effective as such therapies are, a new platform of therapyis needed for treating peripheral arterial disease and more problematiccoronary diseases, such as vulnerable plaque, saphenous vein bypassgraft disease, and diffuse long lesions.

The objective of PDT may be either diagnostic or therapeutic. Indiagnostic applications, the wavelength of light is selected to causethe photoreactive agent to fluoresce, thus yielding information aboutthe tissue without damaging the tissue. In therapeutic applications, thewavelength of light delivered to the tissue treated with thephotoreactive agent causes the photoreactive agent to undergo aphotochemical reaction with oxygen in the localized tissue, to yieldfree radical species (such as singlet oxygen), which cause localizedcell lysis or necrosis. The central strategy to inhibit arterialrestenosis using PDT, for example, is to cause a depletion of vascularsmooth muscle cells, which are a source of neointima cell proliferation(see, Nagae et al., Lasers in Surgery and Medicine 28:381-388, 2001).One of the advantages of PDT is that it is a targeted technique, in thatselective or preferential delivery of the photoreactive agent tospecific tissue enables only the selected tissue to be treated.Preferential localization of a photoreactive agent in areas of arterialinjury, with little or no photoreactive agent delivered to healthyportions of the arterial wall, can therefore enable highly specific PDTablation of arterial tissue.

Light delivery systems for PDT are well known in the art. Delivery oflight from a light source, such as a laser, to the treatment site hasbeen accomplished through the use of a single optical fiber deliverysystem with special light-diffusing tips affixed thereto. Exemplaryprior art devices also include single optical fiber cylindricaldiffusers, spherical diffusers, micro-lensing systems, an over-the-wirecylindrical diffusing multi-optical fiber catheter, and alight-diffusing optical fiber guidewire. Such prior art PDT illuminationsystems generally employ remotely disposed high power lasers or solidstate laser diode arrays, coupled to optical fibers for delivery oflight to a treatment sight. The disadvantages of using laser lightsources include relatively high capital costs, relatively large size,complex operating procedures, and the safety issues inherent whenworking with high power lasers. Accordingly, there is a tremendous needfor a light generating system that requires no lasers, and whichgenerates light at the treatment site. For vascular application of PDT,it would be desirable to provide a light-generating apparatus having aminimal cross-section, a high degree of flexibility, and compatibilitywith a guidewire, so the light-generating apparatus can be delivered tothe treatment site. Such an apparatus should provide a light uniformlyto the treatment area.

For vascular application of PDT, it would be further desirable toprovide a light-generating apparatus configured to be centered within ablood vessel, and which is configured to remove light absorbentmaterial, such as blood, from the light path between the target tissueand the apparatus. Typically, centering of apparatus within a vessel canbe achieved with an inflatable balloon catheter that matches thediameter of the blood vessel when the balloon is inflated. Such devicesdesirably occlude blood flow, enabling the light path to remain clear ofobstructing blood. However, a single balloon is not sufficient to treatlesions in coronary blood vessels that are greater than about 30 mm inlength, because a single inflated balloon may not provide good centeringof the apparatus within such a long section. Therefore, it would bedesirable to provide a light-generating apparatus that is configuredtreat long lesions or long vessel segments.

SUMMARY

The present invention encompasses light generating devices forilluminating portions of vascular tissue to enable PDT to be provided.Each embodiment includes one or more light sources configured to bepositioned inside a body cavity or a vascular system. While the term“light source array” is frequently employed herein, because particularlypreferred embodiments of this invention include multiple light sourcesarranged in a radial or linear configuration, it should be understoodthat a single light source could be employed. Using a plurality of lightsources enables larger treatment areas to be illuminated. Light emittingdiodes (LEDs) are particularly preferred as light sources, althoughother types of light sources can be employed, as will be described indetail below. The light source that is used will be selected based onthe characteristics of a photoreactive agent in connection with whichthe apparatus is intended to be used, since light of incorrectwavelengths will not cause the desired reaction by the photoreactiveagent. Light source arrays can include light sources that provide morethan one wavelength or waveband of light. Linear light source arrays areparticularly useful to treat elongate portions of tissue. Light sourcearrays can also include reflective elements to enhance the transmissionof light in a preferred direction. Each embodiment described herein canbeneficially include expandable members such as inflatable balloons toocclude blood flow (which can interfere with the transmission of lightfrom the light source to the intended target tissue) and to enable theapparatus to be centered in a blood vessel.

In configurations where light is intended to be directed through suchexpandable members to reach target tissue, the expandable members arepreferably constructed from materials that substantially transmit therequired wavelength of light. Bio-compatible polymers having therequired optical characteristics are particularly preferred. Where lightis directed through such expandable members to reach target tissue, afluid used to inflate the expandable members can include additives toenhance the transmission or diffusion of light. In configurations wherean expandable member is disposed proximate to a light source array, thefluid used to expand the member acts as a heat sink to absorb heatgenerated by the light source array. Regularly replacing the fluidwithin the expandable member will enhance the cooling effects.Positioning aids, such as radio-opaque markers, can be included toenable any of the embodiments described in detail below to be properlypositioned with respect to a target area.

A first preferred embodiment is configured to emit light from a distaltip of an elongate flexible body. The first preferred embodimentincludes an elongate flexible body having a distal end and a proximalend, with at least one lumen extending therebetween. A distal portion ofthe first embodiment includes a light source array and a light diffusingelement configured to disperse light from the light source array outwardfrom the distal tip of the apparatus. An electrical lead extends fromthe light source array to at least a proximal end of the elongateflexible body, so that the electrical lead can be coupled to an externalpower source to energize the light source array. A focusing lens and oneor more optical fibers are preferably disposed between the light sourcearray and the light diffusing element. Incorporating a lumen extendingthrough the apparatus enables the apparatus to be advanced to a desiredposition using a guidewire. A radio-opaque material can be includedimmediately adjacent to the light diffusing element to facilitate theproper positioning of the light diffusing element relative to a targetarea. A radially oriented light source array is used in such a firstpreferred embodiment.

A second preferred embodiment is similar to the first preferredembodiment, but further includes a tapered optical fiber, or bundle ofoptical fibers, disposed between the light source array and the lightdiffusing element, such that the light diffusing element has a smallercross sectional area than does the light source array. An inflatableballoon encompasses substantially the entire light diffusing element,and in this embodiment, the elongate flexible body, the light sourcearray, and the tapered optical fiber include an inflation lumen in fluidcommunication with the inflatable balloon. The light source arraypreferably includes reflective elements disposed to maximize theintensity of light directed toward the light diffusing element.

Another preferred embodiment includes an elongate flexible body with alinear light source array coupled to a distal end of the elongateflexible body. The linear light source array must be sufficientlyflexible to enable the apparatus to be advanced through a vascularsystem, and preferably includes a plurality of LEDs attached to aflexible conductive substrate. Encapsulating the light source array in aflexible cover, such as a polymer, will protect the light source arrayfrom damage. Of course, such a cover must be substantially opticallytransparent to the required wavelengths of light. Additives can be addedto the material of the cover to enhance the transmission or diffusion oflight emitted from the light source array. A distal portion is coupledto a distal end of the light source array. The distal portion includesan opening on a sidewall of the distal portion, and an opening on thedistal end of the distal portion, with a lumen extending therebetween toenable the apparatus to be advanced over a guidewire. The linear lightsource array is not configured to include a lumen for a guide wire, sothe opening in the sidewall of the distal portion is required to enablethe apparatus to be used with a guidewire. It should be understood thata lumen for a guidewire can also be included in the polymer cover thatencapsulates the light source array, if it is desired to include aguidewire lumen through each section of the apparatus.

Preferably, this embodiment includes an expandable member disposed tosubstantially encompass the light source array. Accordingly, theelongate flexible body includes an inflation lumen to enable theexpandable member to be inflated. Preferably, each end of the lightsource array is marked with a radio-opaque tag (or some other type ofidentifier) so that the light source array can be properly positionedadjacent to target tissue. The length of the linear array is onlylimited by the length of the expandable member. If the linear array ismade longer than the expandable member, light emitted from that portionof the linear array extending beyond the expandable member will beblocked by blood, and is not likely to reach the target tissue. Asdescribed below, the use of a plurality of expandable members enableslonger linear light sources to be used.

Use of a linear light source array in an apparatus configured in accordwith the present invention requires that the array be sufficientlyflexible to enable the resulting device to be advanced through avascular system. LEDs are sufficiently small and compact, so that whenLEDs are mounted to a flexible conductive substrate, a flexible lightsource array is achieved that meets this requirement. The flexibility ofthe linear light source array can be further enhanced by includingstrain relief elements in the light source array. Also, including aplurality of folds or bends in the flexible conductive substrate willfurther enhance the flexibility of the substrate. The polymer employedto encapsulate the LEDs and conductive substrate is preferably selectedto be both optically transparent to the required wavelength of the lightused, and sufficiently flexible.

Yet another aspect of the present invention is directed to theincorporation of light emitting devices, preferably LEDs, in aguidewire. Such a guidewire is used with a catheter, preferably oneincluding one or more expandable members. A conventional guidewire ismodified to include a conductive core enabling light sources to becoupled to an external power supply, and a plurality of orifices areformed into the guidewire. The orifices extend to the conductive core,so that light sources can be inserted into the orifices and electricallycoupled to the conductive core. Each light source is then electricallycoupled through the conductive core to an external lead that enables acomplete circuit to be achieved to energize the light sources. Theguidewire, external lead, and light sources are then covered with aflexible polymer which should be substantially optically transparent tothe required wavelength or waveband of light, at least where theflexible polymer overlies the light sources.

Still another aspect of the present invention employs at least twoexpandable members to enable a longer portion of a blood vessel to beisolated from blood that would interfere with the transmission of light,compared to the length that can be achieved with a single expandablemember. This embodiment is based on an elongate flexible body includingat least two expandable members, at least two inflation lumens enablingthe expandable members to be inflated, and a lumen for a flushing fluid.A relatively long light source array (i.e., a light source array havinga length greater than a length of any one of the expandable members) isdisposed between a most proximally positioned expandable member and amost distally positioned proximal member. Preferably, radio-opaquemarkers are disposed adjacent to the most proximally positionedexpandable member and the most distally positioned proximal member. Theelongate flexible body includes at least one port coupled in fluidcommunication to the flushing lumen and disposed between the mostproximally positioned expandable member and the most distally positionedproximal member.

In embodiments including two inflation lumens, the apparatus isconfigured such that the most proximal expandable member is in fluidcommunication with the first inflation lumen, while other expandablemembers (those distal to the most proximal expandable member) arecoupled in fluid communication with the other inflation lumen. Once theelongate flexible body is positioned within a blood vessel such that atarget area is disposed between the most proximally positionedexpandable member and the most distally positioned proximal member, themost proximal expandable member is expanded. Then, the flushing fluid isthen introduced into the portion of the blood vessel distal to theactivated expandable member. After sufficient flushing fluid hasdisplaced the blood flow, the more distal expandable member(s) areinflated using the other inflation lumen, thereby isolating the portionof the blood vessel between the inflated expandable members (thatportion being now filled with flushing fluid rather than blood).

In embodiments including an inflation lumen for each expandable member,each expandable member is inflated sequentially, and flushing fluid isalso sequentially introduced into the blood vessel. These embodimentsrequire flushing fluid ports to be disposed between each expandablemember.

It should be noted that inflating a most proximally positionedexpandable member first is appropriate when blood flow in the bloodvessel naturally moves from a proximal portion of the apparatus toward amore distal portion. If the blood flow is in the opposite direction, itwould be appropriate to configure the apparatus to enable the mostdistally positioned expandable member to be inflated first. If eachexpandable member has a dedicated inflation lumen, the order by whichthe various expandable members are activated can be varied as desired.

In regard to the linear light source array used to illuminate the targetarea isolated by the two or more expandable members, in one particularlypreferred embodiment, the linear light source array is incorporated inthe elongate flexible body. Electrical leads used to energize the lightsource array extend through the elongate flexible member and are adaptedto couple to an external power supply. A distal portion is attached to adistal end of the linear light source array, and an orifice is includedin the sidewall of the distal portion, and in the distal end of thedistal portion (with a lumen extending therebetween). These two orificesenable the apparatus to be positioned using a guidewire. Alternatively,the elongate flexible body and the linear light source array can includea guidewire lumen.

In another particularly preferred embodiment, the linear light sourcearray is not part of or attached to the elongate flexible body. Instead,the linear light source array is integrated into a guide wire, producingan illuminated guidewire that includes markings enabling the lightsources on the guidewire to be properly positioned with respect to theportion of the blood vessel isolated by the expandable members.

The embodiments described above are used with a photoreactive agent thatis introduced into the target area prior to the apparatus beingintroduced into the blood vessel. However, it will be understood that ifdesired, the apparatus can optionally include a lumen for delivering aphotoreactive agent into the target area. The resulting embodiments arelikely to be particularly beneficial where uptake of the photoreactiveagent into the target tissues is relatively rapid, so that the apparatusdoes not need to remain in the blood vessel for an extended period oftime while the photoreactive agent is distributed into and absorbed bythe target tissue.

This Summary has been provided to introduce a few concepts in asimplified form that are further described in detail below in theDescription. However, this Summary is not intended to identify key oressential features of the claimed subject matter, nor is it intended tobe used as an aid in determining the scope of the claimed subjectmatter.

DRAWINGS

Various aspects and attendant advantages of one or more exemplaryembodiments and modifications thereto will become more readilyappreciated as the same becomes better understood by reference to thefollowing detailed description, when taken in conjunction with theaccompanying drawings, wherein:

FIG. 1 schematically illustrates a first embodiment of alight-generating apparatus suitable for intra vascular use in accordwith the present invention;

FIG. 2 is a longitudinal cross-sectional view of the light-generatingapparatus of FIG. 1;

FIGS. 3A and 3B are exemplary radial cross-sectional views of twodifferent embodiments of the light-diffusing portion of thelight-generating apparatus of FIG. 1;

FIG. 4A schematically illustrates a second embodiment of alight-generating apparatus suitable for intra vascular use in accordwith the present invention;

FIG. 4B is a longitudinal cross-section view of the light-generatingapparatus of FIG. 2;

FIG. 5 schematically illustrates yet another embodiment of alight-generating apparatus suitable for intra vascular use in accordwith the present invention;

FIG. 6 schematically illustrates the light-generating apparatus of FIG.5 being positioned within a blood vessel;

FIG. 7 schematically illustrates the light-generating apparatus of FIGS.5 and 6 being activated within a blood vessel;

FIG. 8 schematically illustrates a multicolor light array for use in thelight-generating apparatus of FIG. 5;

FIGS. 9A and 9B schematically illustrate configurations of light arraysincluding strain relief features for enhanced flexibility for use in alight-generating apparatus in accord with the present invention;

FIG. 9C is cross-sectional view of a light-generating apparatus inaccord with the present invention, showing one preferred configurationof how the light emitting array is positioned relative to the guidewireused to position the light-generating apparatus;

FIG. 9D schematically illustrates a portion of a light-generatingapparatus in accord with the present invention, showing how in anotherpreferred configuration, the light emitting array is positioned relativeto the guidewire used to position the light-generating apparatus;

FIG. 10 schematically illustrates an embodiment of a light-generatingapparatus in which light emitting elements are incorporated into aguidewire, as the apparatus is being positioned within a blood vessel;

FIG. 11 schematically illustrates another embodiment of alight-generating apparatus, in which light emitting elements areincorporated into a guidewire and which includes an inflatable balloon,showing the apparatus being positioned within a blood vessel;

FIG. 12A schematically illustrates a modified guidewire for use in thelight-generating apparatus of FIGS. 10 and 11;

FIGS. 12B-12D are cross-sectional views of the guidewire of FIG. 12A,showing details of how the light emitting elements are integrated intothe guidewire;

FIG. 13A schematically illustrates still another embodiment of alight-generating apparatus, which includes a plurality of inflatableballoons, as the apparatus is being positioned within a blood vessel;

FIG. 13B is a cross-sectional view of the light-generating apparatus ofFIG. 13A;

FIG. 14A schematically illustrates an alternative configuration of alight-generating apparatus including a plurality of inflatable balloons,as the apparatus is being positioned within a blood vessel;

FIG. 14B is a cross-sectional view of the light-generating apparatus ofFIG. 14A; and

FIG. 15 schematically illustrates a plurality of balloons included witha light-generating apparatus in accord with the present invention.

DESCRIPTION

Figures and Disclosed Embodiments are Not Limiting

Exemplary embodiments are illustrated in referenced Figures of thedrawings. It is intended that the embodiments and Figures disclosedherein are to be considered illustrative rather than restrictive. Nolimitation on the scope of the technology and of the claims that followis to be imputed to the examples shown in the drawings and discussedherein.

Unless otherwise defined, it should be understood that each technicaland scientific term used herein and in the claims that follow isintended to be interpreted in a manner consistent with the meaning ofthat term as it would be understood by one of skill in the art to whichthis invention belongs. The drawings and disclosure of all patents andpublications referred to herein are hereby specifically incorporatedherein by reference. In the event that more than one definition isprovided herein, the explicitly defined definition controls.

Referring to FIG. 1, a light-generating apparatus 1, having a distal end6 and a proximal end 8, is embodied in a catheter having an elongate,flexible body 4 formed from a suitable biocompatible material, such as apolymer or metal. Catheter body 4 includes at least one lumen 18. Whilelumen 18 is shown as centrally disposed within catheter body 4, itshould be understood that lumen 18 can be disposed in other positions,and that other lumens, such as lumens for inflating a balloon ordelivering a fluid (neither separately shown) can also be included anddisposed at locations other than along a central axis of catheter body4. Lumen 18 has a diameter sufficient to accommodate a guidewire andextends between distal end 6 and proximal end 8 of the catheter, passingthrough each portion of light-generating apparatus 1. FIG. 1 is notdrawn to scale, and a majority of light-generating apparatus 1 shown inFIG. 1 relates to elements disposed near distal end 6. It should beunderstood that light-generating apparatus 1 is preferably of sufficientlength to be positioned so that distal end 6 is disposed at a treatmentsite within a patient's body, while proximal end 8 is disposed outsideof the patient's body, so that a physician or surgeon can manipulatelight-generating apparatus 1 with the proximal end.

A light source array 10 includes a plurality of light emitting devices,which are preferably LEDs disposed on conductive traces electricallyconnected to lead 11. Lead 1 extends proximally through lumen 18 and iscoupled to an external power supply and control device 3. While lead 11is shown as a single line, it should be understood that lead 11 includesat least two separate conductors, enabling a complete circuit to beformed that supplies current to the light emitting devices from theexternal power supply. As an alternative to LEDs, other sources of lightmay instead be used, including but not limited to, organic LEDs, superluminescent diodes, laser diodes, and light emitting polymers. In apreferred embodiment, each LED of light source array 10 is encapsulatedin a polymer layer 23. Preferably, collection optics 12 are similarlyencapsulated in polymer layer 23. Light source array 10 is preferablycoupled to collection optics 12, although it should be understood thatcollection optics 12, while preferred, are not required. When present,collection optics 12 are coupled to either a single optical fiber 14, oran optical fiber bundle (not separately shown). Distal to optical fiber14 is a light-diffusing tip 16, which can be implemented using glass orplastic. Light emitted from light source array 10 passes throughcollection optics 12, which focus the light toward optical fiber 14.Light conducted along optical fiber 14 enters diffusing tip 16 at distalend 6 and is scattered uniformly. Preferably, diffusing tip 16 includesa radio-opaque marker 17 to facilitate fluoroscopic placement of distalend 6.

FIG. 2 illustrates a longitudinal cross-section view of light-generatingapparatus 1. Collection optics 12 (e.g., a lens) are bonded to lightsource array 10 and optical fiber 14 by polymer layers 23, and thepolymer layer is preferably an epoxy that is optically transparent tothe wavelengths of light required to activate the photoreactive agentthat is being used. Individual LEDs 10 a and leads 10 b (each couplingto lead 11) can be clearly seen.

FIG. 3A is a radial cross-sectional view of diffusing tip 16, whichincludes one diffusing portion 36 and lumen 18. FIG. 3B is a radialcross-sectional view of an alternative diffusing tip 16 a, whichincludes a plurality of diffusing portions 36 encapsulated in a polymer33, and lumen 18. Polymer 33 preferably comprises an epoxy, and whilesuch an epoxy will likely be optically transparent to the wavelengths oflight required to activate the photoreactive agent being utilized;however, because the light will be transmitted by diffusion portions 36,polymer 33 is not required to be optically transparent to thesewavelengths. In some applications, it may be desirable to prevent lightof any wavelength that can activate the photoreactive agent from exitinga light-generating apparatus other than from its distal end, andpolymers do not transmit such wavelengths can be used to block suchlight.

Turning now to FIG. 4A, another embodiment of a light generatingcatheter is schematically illustrated. A light-generating apparatus 5 issimilarly based a catheter having body 4, including lumen 18, andincludes distal end 6 and proximal end 8. As discussed above, while onlya single lumen configured to accommodate a guidewire is shown, it shouldbe understood that light-generating apparatus 5 can be configured toinclude additional lumens as well (such as those used for ballooninflation/deflation). Note that FIGS. 4A and 4B are not drawn to scale;with distal end 6 being is emphasized over proximal end 8.

Light-generating apparatus 5 includes a light source array 40 comprisinga plurality of LEDs 40 a (seen in phantom view) that are electricallycoupled to lead 11 via leads 40 c. As discussed above, light sourcearray 40 is preferably encapsulated in a light-transmissive polymer 23,or at least, in an epoxy that transmits the wavelengths of lightrequired to activate the photoreactive agent introduced into the targettissue. Positioned immediately behind LEDs 40 a (i.e., proximal of LEDs40 a) is a highly-reflective disk 40 b. Any light emitted from LEDs 40 ain a direction toward proximal end 8 is reflected back by reflectivedisk 40 b towards distal end 6. Additionally, a reflective coating 43(such as aluminum or another reflective material), is applied to theouter surface of body 4 adjacent to light source array 40. Any lightfrom LEDs 40 a directed to the sides (i.e., towards body 4) isredirected by reflective coating 43 towards distal end 6. Reflectivedisk 40 b and reflective coating 43 thus cooperatively maximize theintensity of light delivered through distal end 6.

Light source array 40 is coupled to a focusing lens 42, which in turn,is coupled to an optical fiber bundle 44. Preferably, optical fiberbundle 44 tapers toward distal end 6, as shown in FIGS. 4A and 4B;however, it should be understood that this tapered shape is notrequired. Optical fiber bundle 44 is coupled to a light-diffusing tip46. An expandable member 47 (such as an inflatable balloon) is includedfor centering light-generating apparatus 5 within a blood vessel and foroccluding blood flow past distal end 6 that could reduce the amount oflight delivered to the targeted tissue. The expandable member ispreferably secured to distal end 6 so as to encompass light-diffusingtip 46. Expandable member 47 may be formed from a suitable biocompatiblematerial, such as, polyurethane, polyethylene, fluorinated ethylenepropylene (PEP), polytetrafluoroethylene (PIPE), or polyethyleneterephthalate (PET).

It should be understood that while light source array 40 has beendescribed as including a plurality of LEDs 40 a disposed on conductivetraces electrically connected to lead 11, light source array 40 canalternatively use other sources of light. As noted above, possible lightsources include, but are not limited to, organic LEDs, super luminescentdiodes, laser diodes, and light emitting polymers. While not shown inFIGS. 4A and 4B, it should be understood that light-generating apparatus5 can beneficially incorporate a radio-opaque marker, as described abovein conjunction with light-generating apparatus 1 (in regard toradio-opaque marker 17 in FIGS. 1A and 1B).

FIG. 5 schematically illustrates yet another embodiment of alight-generating catheter in accord with the present invention. Thisembodiment employs a linear light source array configured so that a moreelongate treatment area can be illuminated. While the first and secondembodiments described above use an elongate light diffusing element toilluminate an elongate treatment area, because the light diffusingelements are directing light, not generating light, increasing thelength of the diffusing elements merely distributes the light over agreater area. If diffused over to great an area, insufficientillumination will be provided to each portion of the treatment site. Theembodiment shown in FIG. 5 includes a linear light source array thatenables an elongate treatment area to be illuminated with a greateramount of light than can be achieved using the embodiments shown inFIGS. 1-4B.

Referring to FIG. 5, light-generating apparatus 50 is illustrated. Aswith the embodiments described above (i.e., the light-generatingapparatus shown in FIGS. 1 and 4), light-generating apparatus 50 ispreferably based on a multi-lumen catheter and includes an elongate,flexible body formed from a suitable biocompatible polymer or metal,which includes a distal portion 52 and a proximal portion 54. Aplurality of light emitting devices 53 are disposed on a flexible,conductive substrate 55 encapsulated in a flexible cover 56 (formed ofsilicone or other flexible and light transmissive material). Lightemitting devices 53 and conductive substrate 56 together comprise alight source array. Preferably, light emitting devices 53 are LEDs,although other light emitting devices, such as organic LEDs, superluminescent diodes, laser diodes, or light emitting polymers can beemployed. Each light emitting device 53 preferably ranges from about 1cm to about 10 cm in length, with a diameter that ranges from about 0.5mm to about 5 mm. Flexible cover 56 can be optically transparent or caninclude embedded light scattering elements (such as titanium dioxideparticles) to improve the uniformity of the light emitted fromlight-generating apparatus 50. While not specifically shown, it shouldbe understood that proximal portion 54 includes an electrical leadenabling conductive substrate 56 to be coupled to an external powersupply and control unit, as described above for the embodiments thathave already been discussed.

The array formed of light emitting devices 53 and conductive substrate56 is disposed between proximal portion 54 and distal portion 52, witheach end of the array being identifiable by radio-opaque markers 58 (oneradio-opaque marker 58 being included on distal portion 52, and oneradio-opaque marker 58 being included on proximal portion 54).Radio-opaque markers 58 comprise metallic rings of gold or platinum.Light-generating apparatus 50 includes an expandable member 57 (such asa balloon) preferably configured to encompass the portion oflight-generating apparatus 50 disposed between radio-opaque markers 58(i.e., substantially the entire array of light emitting devices 53 andconductive substrate 56). As discussed above, expandable member 57enables occlusion of blood flow past distal portion 52 and centers thelight-generating apparatus. Where expandable member is implemented as afluid filled balloon, the fluid acts as a heat sink to reduce atemperature build-up caused by light emitting devices 53. This coolingeffect can be enhanced if light-generating apparatus 50 is configured tocirculate the fluid through the balloon, so that heated fluid iscontinually (or periodically) replaced with cooler fluid. Preferably,expandable member 57 ranges in size (when expanded) from about 2 mm to10 mm in diameter. Preferably such expandable members are less than 2 mmin diameter when collapsed, to enable the apparatus to be used in acoronary vessel. Those of ordinary skill will recognize that cathetersincluding an inflation lumen in fluid communication with an inflatableballoon, to enable the balloon to the inflated after the catheter hasbeen inserted into a body cavity or blood vessel are well known. Whilenot separately shown, it will therefore be understood thatlight-generating apparatus 50 (particularly proximal portion 54)includes an inflation lumen. When light emitting devices 53 areenergized to provide illumination, expandable member 57 can be inflatedusing a radio-opaque fluid, such as Renocal 76™ or normal saline, whichassists in visualizing the light-generating portion of light-generatingapparatus 50 during computerized tomography (CT) or angiography. Thefluid employed for inflating expandable member 57 can be beneficiallymixed with light scattering material, such as Intralipid, a commerciallyavailable fat emulsion, to further improve dispersion and lightuniformity.

Light-generating apparatus 50 is distinguished from light-generatingapparatus 1 and 4 described above in that light-generating apparatus 1and 4 are each configured to be positioned within a vessel or otherpassage using a guide wire that extends within lumen 18 substantiallythroughout the apparatus. In contrast, light-generating apparatus 50 ispositioned at a treatment site using a guidewire 51 that does not passthrough the portion of light-generating apparatus 50 that includes thelight emitting devices. Instead, guidewire 51 is disposed external tolight-generating apparatus 50—at least between proximal portion 54 anddistal portion 52. Thus, the part of guidewire 51 that is proximatelight emitting devices 53 is not encompassed by expandable member 57.Distal portion 52 includes an orifice 59 a, and an orifice 59 b.Guidewire 51 enters orifice 59 a, and exits distal portion 52 throughorifice 59 b. It should be understood that guidewire 51 can be disposedexternally to proximal portion 54, or alternatively, the proximalportion can include an opening at its proximal end through which theguidewire can enter the proximal portion, and an opening disposedproximal to light emitting devices 53, where the guidewire then exitsthe proximal portion.

The length of the linear light source array (i.e., light emittingdevices 53 and conductive substrate 56) is only limited by the effectivelength of expandable member 57. If the linear array is made longer thanthe expandable member, light emitted from that portion of the lineararray will be blocked by blood within the vessel and likely not reachthe targeted tissue. As described below in connection with FIGS.13A-14B, the use of a plurality of expandable members enables evenlonger linear light source arrays (i.e., longer than any singleexpandable member) to be used in this invention.

FIG. 6 schematically illustrates a light-generating apparatus 50 a beingpositioned in an artery 61, to provide PDT to post PCTA lesions 60.Light-generating apparatus 50 a is substantially similar tolight-generating apparatus 50 described above, except for includingadditional light emitting devices 53 a disposed in an opposedrelationship with respect to light emitting devices 53, to enable lightoutput from light-generating apparatus 50 a in additional directions.Light-generating apparatus 50 a thus enables lesions on opposing sidesof artery 61 to be treated. In FIG. 6, light-generating apparatus 50 ahas been properly positioned relative to lesions 60 using radio-opaquemarkers 58, so as to treat the lesions with PDT (i.e., the lesions aregenerally disposed between the radio-opaque markers). In FIG. 7,expandable member 57 has been inflated to contact the walls of artery61, thereby centering light-generating apparatus 50 a within artery 61,and occluding blood flow through the artery, to ensure that lightemitted from light emitting devices 53 and 53 a reaches lesions 64 andis not blocked by blood in the artery. Guidewire 51 is removed, and thelight emitting devices are energized to direct light of the requiredwavelengths to lesions 60, which have previously been treated with aphotoreactive agent for diagnostic or therapeutic purposes.

FIGS. 8, 9A, and 9B are enlarged views of light source arrays that canbe used in a light-generating apparatus in accord with the presentinvention. Light source array 80, shown in FIG. 8, includes a pluralityof LEDs 86 a and 86 b that are coupled to a flexible, conductivesubstrate 82. LEDs 86 a emit light of a first color, having a firstwavelength, while LEDs 86 b emit light of a different color, having asecond wavelength. Such a configuration is useful if two differentphotoreactive agents have been administered, where each differentphotoreactive agent is activated by light of a different wavelength.Light source array 80 also includes one or more light sensing elements84, such as photodiodes or a reference LED, similarly coupled toflexible, conductive substrate 82. Each light sensing element 84 may becoated with a wavelength-specific coating to provide a specific spectralsensitivity, and different light sensing elements can have differentwavelength-specific coatings. While light source array 80 is configuredlinearly, with LEDs on only one side (as the array in light-generatingapparatus 50 a of FIG. 5), it will be understood that different colorLEDs and light sensing elements can be beneficially included in any ofthe light source arrays described herein.

Because the light source arrays of the present invention are intended tobe used in flexible catheters inserted into blood vessels or other bodypassages, it is important that the light source arrays be relativelyflexible, particularly where a light source array extends axially alongsome portion of the catheter's length. Clearly, the longer the lightsource array, the more flexible it must be. Light source arrays 10 and40 (FIGS. 1A/1B, and 4A/4B, respectively) are configured in a radialorientation, and light emitted form the light sources in those arrays isdirected to the distal end of the respective catheters (light-generatingapparatus 1 and 4). Because light source arrays 10 and 40 do not extendaxially along a substantial portion of their respective catheters, therelatively flexibility of light source arrays 10 and 40 is lessimportant. However, light source array 80 (FIG. 8), and the light sourcearrays of light-generating apparatus 50 and 50 a (FIGS. 5 and 6,respectively), are linearly configured arrays that extend axially alonga more significant portion of their respective catheters. A requiredcharacteristic of a catheter for insertion into a blood vessel is thatthe catheter be sufficiently flexible to be inserted into a vessel andadvanced along an often tortuous path. Thus, light source arrays thatextend axially along a portion of a catheter can unduly inhibit theflexibility of that catheter. FIGS. 9A and 9B schematically illustrateaxially extending light source arrays that include strain relieffeatures that enable a more flexible linear array to be achieved.

FIG. 9A shows a linear array 88 a having a plurality of light emittingsources 90 (preferably LEDS, although other types of light sources canbe employed, as discussed above) mounted to both a first flexibleconductive substrate 92 a, and a second flexible conductive substrate 92b. Flexible conductive substrate 92 b includes a plurality of strainrelief features 93. Strain relief features 93 are folds in the flexibleconductive substrate that enable a higher degree of flexibility to beachieved. Note that first flexible conductive substrate 92 a is notspecifically required and can be omitted. Further, strain relieffeatures 93 can also be incorporated into first flexible conductivesubstrate 92 a.

FIG. 9B shows a linear array 88 b having a plurality of light emittingsources 90 mounted on a flexible conductive substrate 92 c. Note thatflexible conductive substrate 92 c has a crenellated configuration. Asshown, light emitting sources 90 are disposed in each “notch” of thecrenellation. That is, light emitting sources 90 are coupled to both anupper face 93 a of flexible conductive substrate 92 c, and a lower face93 b of flexible conductive substrate 92 c. Thus, when light emittingsources 90 are energized, light is emitted generally outwardly away fromboth upper surface 93 a and lower surface 93 b. If desired, lightemitting sources 90 can be disposed on only upper surface 93 a or onlyon lower surface 93 b (i.e., light emitting sources can be disposed inevery other “notch”), so that light is emitted generally outwardly awayfrom only one of upper surface 93 a and lower surface 93 b. Thecrenellated configuration of flexible conductive substrate 92 c enablesa higher degree of flexibility to be achieved, because each crenellationacts as a strain relief feature.

External bond wires can increase the cross-sectional size of an LEDarray, and are prone to breakage when stressed. FIGS. 1A and 1Billustrate leads 10 b that are exemplary of such external bond wires.FIG. 9C schematically illustrates a flip-chip mounting technique thatcan be used to eliminate the need for external bond wires on LEDs 94that are mounted on upper and lower surfaces 93 c and 93 d(respectively) of flexible conductive substrate 92 d to produce a lightsource array 97. Any required electrical connections 95 pass throughflexible conductive substrate 92 d, as opposed to extending beyondlateral sides of the flexible conductive substrate, which would tend toincrease the cross-sectional area of the array. Light source array 97 isshown encapsulated in a polymer layer 23. A guidewire lumen 98 a isdisposed adjacent to light source array 97. An expandable balloon 99encompasses the array and guidewire lumen. Note that either, but notboth, polymer layer 23 and expandable balloon 99 can be eliminated(i.e., if the expandable balloon is used, it provides protection to thearray, but if not, then the polymer layer protects the array).

FIG. 9D shows a linear array 96 including a plurality of light emittingsources (not separately shown) that spirals around a guidewire lumen 98b. Once again, balloon 99 encompasses the guidewire lumen and the array,although if no balloon is desired, a polymer layer can be used instead,as noted above. For each of the implementations described above, thearray of light sources may comprise one or more LEDs, organic LEDs,super luminescent diodes, laser diodes, or light emitting polymersranging from about 1 cm to about 10 cm in length and having a diameterof from about 1 mm to about 2 mm.

Turning now to FIG. 10, a light-generating apparatus 100 is shown as theapparatus is being positioned in a blood vessel 101, to administer PDTto treatment areas 108. Light-generating apparatus 100 is simpler inconstruction than light-generating apparatus 1, 4, 50, and 50 a (each ofwhich is based on a catheter), because light-generating apparatus 100 isbased on a guidewire. Light-generating apparatus 100 includes a mainbody 102, a light source array 104, and a spring tip 106. Main body 102is based on a conventional guidewire, preferably having a diameterranging from about 0.10 inches to about 0.060 inches. However, main body102 is distinguishable from a conventional guidewire because main body102 includes electrical lead 105. Spring tip 106 is also based on aconventional guidewire spring tip. Light source array 104 includes aplurality of light emitting devices 107, each electrically coupled tolead 105 (alternatively, each light emitting device is coupled to aflexible conductive substrate, that is in turn electrically coupled tolead 105). While not separately shown, it should be understood thatradio-opaque markers can be included at each end of light source array104, thereby enabling the light source array to be properly positionedrelative to treatment areas 108.

In FIG. 11, light-generating apparatus 100 has been inserted into aballoon catheter 112, and the combination of balloon catheter 112 andlight-generating apparatus 100 is shown being positioned in blood vessel101, also to administer PDT to treatment areas 108. Balloon 114 has beeninflated to contact the walls of blood vessel 101, thereby centering thecombination of balloon catheter 112 and light-generating apparatus 100within blood vessel 101 and occluding blood flow that could allow bloodto block light emitted from light emitting devices 107 from reachingtreatment areas 108. As discussed above, the fluid used to inflate theballoon should readily transmit the wavelengths of light required toactivate the photoreactive agent(s) used to treat treatment areas 108.As described above, additives can be added to the fluid to enhance lighttransmission and diffusion. The fluid will also act as a heat sink toabsorb heat generated by light emitting devices 107, and the beneficialeffect of the fluid as a coolant can be enhanced by regularlycirculating the fluid through the balloon.

FIGS. 12A-12D provide details showing how light emitting devices can beintegrated into guidewires. Referring to FIG. 12A, a solid guidewire 120includes a conductive core 124 and a plurality of compartments 121formed in the guidewire around the conductive core. Conductive core 124is configured to be coupled to a source of electrical energy, so thatelectrical devices coupled to conductive core 124 can be selectivelyenergized by current supplied by the source. Compartments 121 can beformed as divots, holes, or slots in guidewire 120, using any of aplurality of different processes, including but not limited to,machining, and laser cutting or drilling. Compartments 121 can be variedin size and shape. As illustrated, compartments 121 are arrangedlinearly, although such a linear configuration is not required.Preferably, each compartment 121 penetrates sufficiently deep intoguidewire 120 to enable light emitting devices 122 to be placed into thecompartments and be electrically coupled to the conductive core, asindicated in FIG. 12B. A conductive adhesive 123 can be beneficiallyemployed to secure the light emitting devices into the compartments andprovide the electrical connection to the conductive core. Of course,conductive adhesive 123 is not required, and any suitable electricalconnections can alternatively be employed. Preferably, LEDs are employedfor the light emitting devices, although as discussed above, other typesof light sources can be used. If desired, only one compartment 121 canbe included, although the inclusion of a plurality of compartments willenable a light source array capable of simultaneously illuminating alarger treatment area to be achieved.

Once light emitting devices 122 have been inserted into compartments 121and electrically coupled to conductive core 124, a second electricalconductor 126, such as a flexible conductive substrate or a flexibleconductive wire, is longitudinally positioned along the exterior ofguidewire 120, and electrically coupled to each light emitting device122 using suitable electrical connections 128, such as conductiveadhesive 123 as (illustrated in FIG. 12B) or wire bonding (asillustrated in FIG. 12C). Guidewire 120 (and conductor 126) is thencoated with an insulating layer 129, to encapsulate and insulateguidewire 120 (and conductor 126). The portion of insulating layer 129covering light emitting devices 122 must transmit light of thewavelength(s) required to activate the photoreactive agent(s). Otherportions of insulating layer 129 can block such light transmission,although it likely will be simpler to employ a homogenous insulatinglayer that transmits the light. Additives can be included in insulatinglayer 129 to enhance the distribution of light from the light emittingdevise, generally as described above.

As already noted above, using a plurality of expandable members enablesa linear light source array that is longer than any one expandablemember to be employed to illuminate a treatment area that is also longerthan any one expandable member. FIGS. 13A, 13B, 14A, and 14B illustrateapparatus including such a plurality of expandable members. FIGS. 13Aand 13B show an apparatus employed in connection with an illuminatedguidewire, while FIGS. 14A and 14B illustrate an apparatus that includesa linear light source array combined with the plurality of expandablemembers. In each embodiment shown in these FIGURES, a relatively longlight source array (i.e., a light source array having a length greaterthan a length of any expandable member) is disposed between a mostproximally positioned expandable member and a most distally positionedproximal member.

FIG. 13A schematically illustrates a light-generating apparatus 131 fortreating relatively long lesions (i.e., lesions of about of 60 mm inlength or longer) in a blood vessel 137. Light-generating apparatus 131is based on a multi-lumen catheter 130 in combination with anilluminated guidewire 135 having integral light emitting devices.Multi-lumen catheter 130 is elongate and flexible, and includes aplurality of expandable members 133 a-133 d. While four such expandablemembers are shown, alternatively, more or fewer expandable members canbe employed, with at least two expandable members being particularlypreferred. As discussed above, such expandable members occlude bloodflow and center the catheter in the vessel. Multi-lumen catheter 130 andexpandable members 133 a-133 d preferably are formed from a suitablebio-compatible polymer, including but not limited to polyurethane,polyethylene, PEP, PTFE, or PET. Each expandable member 133 a-133 dpreferably ranges from about 2 mm to about 10 mm in diameter and fromabout 1 mm to about 60 mm in length. When inflated, expandable members133 a-133 d are pressurized from about 1 atmosphere to about 16atmospheres. It should be understood that between expandable member 133a and expandable member 133 d, multi-lumen catheter 130 is formed of aflexible material that readily transmits light of the wavelengthsrequired to activate the photoreactive agent(s) with whichlight-generating apparatus 131 will be used. Bio-compatible polymershaving the required optical characteristics can be beneficiallyemployed. As discussed above, additives such as diffusion agents can beadded to the polymer to enhance the transmission or diffusion of light.Of course, all of multi-lumen catheter 130 can be formed of the samematerial, rather than just the portions between expandable member 133 aand expandable member 133 d. Preferably, each expandable member 133a-133 d is similarly constructed of a material that will transmit lighthaving the required wavelength(s). Further, any fluid used to inflatethe expandable members should similarly transmit light having therequired wavelength(s).

Referring to the cross-sectional view of FIG. 13B (taken along linessection lines A-A of FIG. 13A), it will be apparent that multi-lumencatheter 130 includes an inflation lumen 132 a in fluid communicationwith expandable member 133 a, a second inflation lumen 132 b in fluidcommunication with expandable members 133 b-c, a flushing lumen 134, anda working lumen 136. If desired, each expandable member can be placed influid communication with an individual inflation lumen. Multi-lumencatheter 130 is configured such that flushing lumen 134 is in fluidcommunication with at least one port 138 (see FIG. 13A) formed throughthe wall of multi-lumen catheter 130. As illustrated, a single port 138is disposed between expandable member 133 a and expandable member 133 band functions as explained below.

Once multi-lumen catheter 130 is positioned within blood vessel 137 sothat a target area is disposed between expandable member 133 a andexpandable member 133 d, inflation lumen 132 a is first used to inflateexpandable member 133 a. Then, the flushing fluid is introduced intoblood vessel 137 through port 138. The flushing fluid displaces blooddistal to expandable member 133 a. After sufficient flushing fluid hasdisplaced the blood flow, inflation lumen 132 b is used to inflateexpandable members 133 b, 133 c, thereby trapping the flushing fluid inportions 137 a, 137 b, and 137 c of blood vessel 137. The flushing fluidreadily transmits light of the wavelength(s) used in administering PDT,whereas if blood were disposed in portions 137 a, 137 b, and 137 c ofblood vessel 137, light transmission would be blocked. An alternativeconfiguration would be to provide an inflation lumen for each expandablemember, and a flushing port disposed between each expandable member. Theexpandable members can then be inflated, and each distal region can beflushed, in a sequential fashion.

A preferred flushing fluid is saline. Other flushing fluids can be used,so long as they are non toxic and readily transmit light of the requiredwavelength(s). As discussed above, additives can be included in flushingfluids to enhance light transmission and dispersion relative to thetarget tissue. Working lumen 136 is sized to accommodate light emittingguidewire 135, which can be fabricated as described above. Multi-lumencatheter 130 can be positioned using a conventional guidewire that doesnot include light emitting devices. Once multi-lumen catheter 130 isproperly positioned and the expandable members are inflated, theconventional guidewire is removed and replaced with a light emittingdevice, such as an optical fiber coupled to an external source, or alinear array of light emitting devices, such as LEDs coupled to aflexible conductive substrate. While not specifically shown, it will beunderstood that radio-opaque markers such as those discussed above canbe beneficially incorporated into light-generating apparatus 131 toenable expandable members 133 a and 133 d to be properly positionedrelative to the target tissue.

Still another embodiment of the present invention is light-generatingapparatus 141, which is shown in FIG. 14A disposed in a blood vessel147. Light-generating apparatus 141 is similar to light-generatingapparatus 131 describe above, and further includes openings for using anexternal guide wire, as described above in connection with FIG. 5. Anadditional difference between this embodiment and light-generatingapparatus 131 is that where light emitting devices were not incorporatedinto multi-lumen catheter 130 of light-generating apparatus 131, a lightemitting array 146 is incorporated into the catheter portion oflight-generating apparatus 141. FIGS. 1, 2, and 5 show exemplaryconfigurations for incorporating light emitting devices into a catheter.

Light-generating apparatus 141 is based on an elongate and flexiblemulti-lumen catheter 140 that includes light emitting array 146 and aplurality of expandable members 142 a-142 d. Light emitting array 146preferably comprises a linear array of LEDs. As noted above, while fourexpandable members are shown, more or fewer expandable members can beemployed, with at least two expandable members being particularlypreferred. The materials and sizes of expandable members 142 a-142 d arepreferably consistent with those described above in conjunction withmulti-lumen catheter 130. The walls of multi-lumen catheter 140proximate to light emitting array 146 are formed of a flexible materialthat does not substantially reduce the transmission of light of thewavelengths required to activate the photoreactive agent(s) with whichlight-generating apparatus 141 will be used. As indicated above,bio-compatible polymers having the required optical characteristics canbe beneficially employed, and appropriate additives can be used.Preferably, each expandable member is constructed of a material andinflated using a fluid that readily transmit light of the requiredwavelength(s).

Referring to the cross-sectional view of FIG. 14B (taken along sectionline B-B of FIG. 14A), it can be seen that multi-lumen catheter 140includes an inflation lumen 143 a in fluid communication with expandablemember 142 a, a second inflation lumen 143 b in fluid communication withexpandable members 142 b-c, a flushing lumen 144, and a working lumen149. Again, if desired, each expandable member can be placed in fluidcommunication with an individual inflation lumen. Multi-lumen catheter140 is configured so that flushing lumen 144 is in fluid communicationwith a port 148 (see FIG. 14A) formed in the wall of multi-lumencatheter 140, which enables a flushing fluid to be introduced intoportions 147 a-147 c of blood vessel 147 (i.e., into those portionsdistal of expandable member 142 a). Those portions are isolated usinginflation lumen 143 b to inflate expandable members 142 b-142 d. Theflushing fluid is selected as described above. Working lumen 149 issized to accommodate light emitting array 146. Electrical leads 146 bwithin working lumen 149 are configured to couple to an external powersupply, thereby enabling the light source array to be selectivelyenergized with an electrical current. A distal end 139 of multi-lumencatheter 140 includes an opening 160 a in the catheter side wallconfigured to enable guidewire 145 (disposed outside of multi-lumencatheter 140) to enter a lumen (not shown) in the distal end of thecatheter that extends between opening 160 a and an opening 160 b,thereby enabling multi-lumen catheter 140 to be advanced over guidewire145.

FIG. 15 shows an alternative embodiment of the light-generatingapparatus illustrated in FIGS. 13A, 13B, 14A, and 14B. Alight-generating apparatus 150 in FIG. 15 is based on a multi-lumencatheter having an elongate, flexible body 154 formed from a suitablebio-compatible polymer and expandable members 152 a-152 d. As indicatedabove, at least two expandable members are particularly preferred. Thedifference between light-generating apparatus 150 and light-generatingapparatus 131 and 141, which were discussed above, is that theexpandable members in light-generating apparatus 150 are fabricated asintegral portions of body 154, while the expandable members oflight-generating apparatus 131 and 141 are preferably implemented asseparate elements attached to a separate catheter body.

Although the concepts disclosed herein have been described in connectionwith the preferred form of practicing them and modifications thereto,those of ordinary skill in the art will understand that many othermodifications can be made thereto within the scope of the claims thatfollow. Accordingly, it is not intended that the scope of these conceptsin any way be limited by the above description, but instead bedetermined entirely by reference to the claims that follow.

1. A method for using photodynamic therapy to treat vascular tissue,comprising the steps of: (a) providing a vascular illumination apparatuscomprising: (i) an elongate, flexible body having a proximal end, adistal end, and at least one lumen; and (ii) a light source elementdisposed adjacent to the distal end of the elongate, flexible body, thelight source element, when energized, emitting light having acharacteristic emission waveband; (b) administering a photoreactiveagent to target vascular tissue in a patient, the photoreactive agenthaving a characteristic absorption waveband corresponding to thecharacteristic emission waveband of the light source element; (c)advancing the vascular illumination apparatus through the vascularsystem of the patient until the light source element is disposedadjacent to the vascular target tissue; and (d) energizing the lightsource element to administer light to the vascular target tissue, theapplication of light to the vascular target tissue resulting in at leastone of a therapeutic effect and generation of diagnostic data.
 2. Themethod of claim 1, wherein before the step of energizing the lightsource element, further comprising the step of centering the vascularillumination apparatus within a blood vessel that includes the vasculartarget tissue.
 3. The method of claim 1, wherein before the step ofenergizing the light source element, further comprising the step ofdisplacing a bodily fluid disposed between the light source element andthe vascular target tissue, thereby preventing the bodily fluid frominterfering with the transmission of light from the light source elementto the target tissue.
 4. The method of claim 3, wherein the step ofdisplacing the bodily fluid disposed between the light source elementand the target tissue before the step of energizing the light sourceelement comprises the step of inflating an expandable member thatsubstantially encompasses the light source element until the expandablemember contacts the walls of the vascular lumen adjacent to the targettissue, thereby displacing bodily fluid that could interfere with thetransmission of light from the light source element to the targettissue.
 5. The method of claim 3, wherein the step of displacing thebodily fluid disposed between the light source element and the targettissue before the step of energizing the light source element comprisesthe steps of: (a) inflating a first expandable member disposed distal ofthe light source element and a second expandable member disposedproximal of the light source element until the first and the secondexpandable members contact the walls of the vascular lumen adjacent tothe target tissue; and (b) replacing the bodily fluid trapped betweenthe first expandable member and the second expandable member with aflush fluid.
 6. The method of claim 1, further comprising the step ofdiffusing the light emitted by the light source element that isadministered to the vascular target tissue.
 7. The method of claim 1,further comprising the step of emitting light from the light sourceelement along a linear path.
 8. The method of claim 1, furthercomprising the step of guiding the elongate, flexible body over a guidewire that includes the light source element.